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OBJECTIVE@#To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis.@*METHODS@#A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities.@*RESULTS@#DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01).@*CONCLUSION@#DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.
Subject(s)
Mice , Animals , Tumor Suppressor Protein p53/metabolism , Endothelial Cells/metabolism , Exosomes/metabolism , bcl-2-Associated X Protein/metabolism , Myocardium/metabolism , Myocardial Infarction/drug therapy , Apoptosis , MicroRNAs/metabolismABSTRACT
OBJECTIVE@#To assess the trends in characteristics, treatments, and outcomes of acute myocardial infarction (AMI) patients in tertiary Chinese medicine (CM) hospitals in China between 2006 and 2013.@*METHODS@#This retrospective study was based on two nationwide epidemiological surveys of AMI in tertiary CM hospitals during 2 years (2006 and 2013). Patients admitted to the hospital for AMI were enrolled. Hospital records were used as the data source. Case data were derived regarding baseline characteristics, treatments, and outcomes of patients to assess changes from 2006 to 2013. Logistic regression was used to analyze the relationship between prognosis, general influencing factors of disease, and various treatment measures.@*RESULTS@#Totally 26 tertiary CM hospitals in 2006 and 29 tertiary CM hospitals in 2013 (18 were repetitive) were surveyed. A total of 2,311 patients with AMI were enrolled (1,094 cases in 2006 and 1,217 cases in 2013). From 2006 to 2013, the mean age did not significantly change, but the proportion of patients younger than 65 years increased. The prevalence of risk factors such as hypertension, diabetes, and hyperlipidemia also increased. Significant increases were observed in primary percutaneous coronary intervention [20.48% (2006) vs. 24.90% (2013)] and revascularization [36.11% (2006) vs. 52.42% (2013)]. In-hospital mortality decreased from 11.15% in 2006 to 10.60% in 2013. A mortality logistic regression analysis identified reperfusion therapy [odds ratio (OR), 0.222; 95% confidence interval (CI), 0.106-0.464], Chinese patent medicines (OR, 0.394; 95% CI, 0.213-0.727), and CM decoctions (OR, 0.196; 95% CI, 0.109-0.353) as protective factors.@*CONCLUSION@#Reperfusion and revascularization capabilities of tertiary CM hospitals have improved significantly, but in-hospital mortality has not significantly decreased. Efforts are needed to improve medical awareness of AMI and expand the use of CM to reduce in-hospital mortality in China.
ABSTRACT
<p><b>OBJECTIVE</b>To survey the treatment status and clinical features of hospitalized patients with acute myocardial infarction (AMI) of 13 hospitals in Beijing in 2005.</p><p><b>METHODS</b>Uniform questionnaires were used to register AMI patients hospitalized from January 1 to December 31, 2005 in the 13 hospitals including traditional Chinese medicine (TCM) hospitals (n = 6) and western medicine hospitals (WM, n = 7) from Beijing. A total of 1663 AMI patients were registered (1366 cases in WM hospitals and 297 cases in TCM hospitals). An Access database was established and patient information was input, the clinical features and treatment status of hospitalized AMI patients were analyzed.</p><p><b>RESULTS</b>The mean age was (63.9 +/- 12.8) years old [(62.8 +/- 12.8) years for WM Hospitals and (69.1 +/- 11.8) years for TCM hospitals, P < 0.05], male to female ratio was 2.4:1 (2.7:1 for WM hospitals and 1.6:1 for TCM hospitals, P < 0.05). The median time to hospital was 14 hours in TCM hospitals and 11 hours in WM hospitals (P > 0.05). Incidences of history of cerebrovascular disease, high blood pressure, diabetes, hyperlipidemia and complications such as in-patient arrhythmia, cardiac insufficiency, cardiogenic shock were significantly higher in TCM hospitals than in WM hospitals. The total mortality of 1663 AMI cases was 8.2% (15.8% in TCM hospitals vs. 6.6% in WM hospitals, P < 0.01). The reperfusion rate including emergency PCI and thrombolytic therapy rate was 31.3% in 13 hospitals (33.3% in WM hospitals vs. 21.9% in TCM hospitals, P < 0.05). Percent of guideline recommend drug use for AMI was as follows: aspirin 93.6%, ACEI and ARB 85.1%, beta-blocker 78.7%, low molecular weight heparin 85.4%, statins 74.7%.</p><p><b>CONCLUSIONS</b>Reperfusion therapy and guideline recommended drugs were widely used although there was a need for further improvement. The hospitalized mortality showed a downward trend compared with results from five years ago, patients in TCM hospitals had an independent clinical features.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Hospital Mortality , Hospitalization , Hospitals , Inpatients , Medicine, Chinese Traditional , Myocardial Infarction , Therapeutics , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To investigate and analyze the therapeutic level and the existing problems on acute myocardial infarction (AMI) management in Beijing.</p><p><b>METHODS</b>We collected clinic data of 1242 AMI patients from 12 hospitals in Beijing, from January 2000 to March 2001, using a uniformed questionnaire, and evaluated the status of the diagnosis and treatment of AMI according to the Chinese guidelines issued on Decmeber 2001. Corresponding factors which influencing the mortality were also analyzed by one-way factor and multiple factors analysis methodologies.</p><p><b>RESULTS</b>The mean age of the 1242 AMI patients was 63.0 years old and about one third of them were under 55 years old. In hospitals, the total mortality was 9.10%. 37.9% of the patients had received therapy of the intravenous thrombolysis and emergency PCI with a total rate of reperfusion therapy as 56.0%. The in-hospital rates of drug use were as follows: Nitrates 90.0%, Aspirin 87.8%, heparin 88.7%, beta-blockers 73.4%, angiotensin converting enzyme inhibitors(ACEI) 77.6%, lipid regulating agents 43.6%. The rate of intravenous therapy of TCM by promoting the blood circulation and supplementing the vital energy was 30.5%. Results from multiple factors analysis showed that the compositive factors which could lower the mortality were reperfusion therapy,lipid regulating agents, intravenous therapy of TCM, beta-blockers, ACEI, lower molecule heparin and digitalis.</p><p><b>CONCLUSION</b>Data from this study showed that there still existed a gap between clinical management on AMI and the guideline in Beijing. To set up a straightway passage of reperfusion therapy, to become more standardized to follow the guideline in undertaking the medical treatment practice, and to go deep into discuss the status of TCM on AMI management seemed the important tasks we are facing.</p>